In Situ Expression of cagA and Risk of Gastroduodenal Disease in Helicobacter pylori–infected Children

Abstract

Gastroduodenal disease is more common among adults and children with cagA+ H. pylori infection, but disease severity varies among those infected with cagA+ strains. We examined whether cagA in situ expression can predict disease manifestations among H. pylori infected children. Fifty-one children were selected from 805 patients with abdominal symptoms who underwent esophagogastroduodenoscopy with gastric biopsies. Endoscopic and histologic gastritis were scored and H. pylori colonization was quantified by Genta stain and in situ hybridization expression of 16S rRNA and cagA. Endoscopy was either normal (n=14) or demonstrated nodularity (n=18), gastric ulcer (GU, n=8) or duodenal ulcer (DU, n=11). H. pylori was present in 7, 18, 6, and 10 children, respectively. Expression of 16S rRNA and cagA were significantly higher in children with ulcer compared to normal. The fraction of H. pylori bacteria expressing cagA in situ was higher in children with ulcer compared to those with endoscopic nodularity (p<0.05). Thus, cagA in situ expression is increased in H. pylori infected children with peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease during childhood. Determination of in situ expression of cagA complements traditional isolation and in vitro testing of single colony isolates. • JR and MG designed and performed the study, analyzed the data and revised the manuscript; CSM mentored JR and MG, supervised performance and analysis of in situ hybridization studies, and revised the manuscript; HL designed and validated the probes used for in situ hybridization studies, and revised the manuscript; CO performed the statistical analysis and revised the manuscript; ERP reviewed and graded histopathology sections and revised the manuscript; CS helped in the analysis of the clinical data and revised the manuscript; and AD closely supervised and participated in the design and performance of all the steps of the study, and revised the manuscript.

Prevalence of Infection With Caga-Positive Helicobacter Pylori Strains Among Children and Adolescents in Southern Brazil

“…Several authors (4,20,28) argue that cagA polymorphisms may affect its biological function, justifying the lack of association between the presence of the gene and a more severe clinical presentation, as was observed in this and other studies (13,20,28) . Furthermore, the mere presence of a gene does not suffice; it must be expressed in the host for its role in pathogenesis to be fully evaluated (25) . Finally, the clinical heterogeneity of our sample, which included patients with various gastrointestinal symptoms and over a wide age range, can be considered a major limitation of this study.…”

Clinical Relevance of the cagA,vacA and babA2 Virulence Factors ofHelicobacter pylori in Egyptian Patients with Gastroduodenal Diseases.

“…The cause of the variability in these studies is unknown, but may be related to differences in methodology, study populations, bacterial strains [76] or may be due to the different state of cagA expression as patients who are cagA positive by PCR may have a relatively low expression level of the virulence gene in situ and this extend the pathogenesis of PUD by demonstrating the importance of cagA expression at the cellular level in addition to traditional isolation [77].…”

Relationship Between Drug Resistance and cagA Gene in Helicobacter pylori

“…Suspensions of 3-day old cultures were prepared in sterile normal saline to match with No. 4 McFarland standard (11). The disks of antibiotics (MAST Co., England) including clarithromycin (15 µg), amoxicillin (25 µg), and metronidazole (5 µg) were placed on the inoculated plates and incubated for 72 hours.…”

“…The virulence factor that has attracted most of the interests is the cytotoxinassociated gene A (cagA), which encodes the CagA protein and the cellular effects of CagA may clarify why patients infected with cagA strains, usually have higher inflammatory responses and level of proinflammatory cytokines. Thus, these gastric mucosal responses induce the peptic ulcer diseases, precancerous lesions, and cancer in adults (4). Approximately 60% of H. pylori strains isolated in Western countries carry cag pathogenesity island (cag PAI), whereas almost all of the isolates from East Asia are cag PAI-positive (5).…”